BACKGROUND:There is limited data on immune checkpoint inhibitor (ICI) use in patients with non-small cell lung cancer (NSCLC) and known pericardial effusions. METHODS:This international multi-center observational retrospective study included patients with advanced NSCLC with or without pericardial effusions receiving ICIs. Immune-related adverse events (irAEs) were graded per CTCAE v5.0. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Cox proportional hazards multivariable models assessed the association between survival outcomes and clinicopathologic variables, and an inverse probability of treatment weighting (IPTW) model compared outcomes between the two groups. RESULTS:A total of 1248 patients with advanced NSCLC treated with ICIs across 13 institutions were included. Of these, 85 patients (6.8%) had pre-existing pericardial effusions. Compared to controls, patients with pericardial effusions were younger (median age 63 vs 67 years, P = .007), diagnosed more frequently with PD-L1 positive tumors (96% vs 76%, P < .001), and had a higher median number of baseline metastatic sites (3 vs 1, P < .001). IrAEs were similar between both groups (42% vs 38%), and no cardiac irAEs occurred in patients with pericardial effusions. PFS (median 5.6 vs 4.6 months, P = .3) and OS (median 10.2 vs 14.7 months, P = .50) were not statistically different between patients with pericardial effusions and the controls, respectively. In both multivariable and IPTW models, pericardial effusions were not associated with PFS or OS. CONCLUSIONS:Among patients with NSCLC and pre-existing pericardial effusions, ICIs demonstrate meaningful clinical benefit similar to those without effusions, with no new cardiac or severe toxicities.

Introduction Use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for control of type 2 diabetes and cardiovascular disease (CVD) risk reduction is increasing. Given the established link between obesity and multiple cancers, there is growing interest in the potential effects of GLP-1RAs on cancer risk reduction. This systematic literature review and meta-analysis evaluated the association between GLP-1RA use and cancer incidence. Methods We conducted literature searches in MEDLINE and EMBASE databases, covering publications up to September 17th, 2025. Our review included studies among adults receiving GLP-1RAs for any indication that reported effects on cancer incidence of any type. Results Among 1,644 unique citations identified, 139 studies met the inclusion criteria for full-text review. After study exclusion, a total of 78 observational studies were included in the review and meta-analysis. GLP-1RA use was associated with statistically significant reductions in cancer risk for 10 of 13 obesity-associated cancers, specifically colorectal, endometrial, esophageal, gallbladder, liver, ovarian, pancreatic and stomach cancers along with meningioma and multiple myeloma. Compared to insulin specifically, GLP-1RAs provided protective effects against cancer of the colorectum (RR: 0.54, 95% CI: 0.44, 0.66), liver (RR: 0.35, 95% CI: 0.20, 0.62), and pancreas (RR: 0.41, 95% CI: 0.36, 0.48). The risk of developing thyroid cancer was slightly elevated, but not statistically significant, among GLP-1RA users (RR: 1.09, 95% CI: 0.98, 1.21). Conclusions Pooled estimates of observational studies suggest notable reductions in cancer incidence for several obesity-associated cancers. As GLP-1RA use increases, ongoing safety monitoring and long-term real-world data are essential. The potential role of GLP-1RAs in cancer risk reduction warrants further investigation through large-scale RCTs, alongside balanced risk-benefit discussions with patients.

INTRODUCTION:A positive result from a multi-target stool DNA (mt-sDNA) test, fecal immunochemical test (FIT), or fecal occult blood test (FOBT) requires a timely follow-up colonoscopy (FU-CY) to minimize colorectal cancer (CRC) incidence and reduce CRC-related mortality. This study aimed to assess differences in FU-CY adherence between patients who received a positive mt-sDNA or FIT/FOBT result by payer type. METHODS:This retrospective analysis utilized a large national claims database linked to the Exact Sciences Laboratories database, covering over 20 million individuals. Eligible patients were 45-75 years old with a positive result between 1 January 2017 and 30 June 2022, with the first test result serving as the index date. Primary outcomes included FU-CY adherence and time to colonoscopy completion. RESULTS:A total of 362,646 (mt-sDNA n = 292,300; FIT/FOBT n = 70,346) patients were identified. Overall adherence to FU-CY was significantly (p < .001) higher for the mt-sDNA test cohort (77.1%) compared to the FIT/FOBT cohort (45.1%). Among payer types, mt-sDNA test adherence was highest for commercial insurance (80.7%) and lowest for Medicaid (69.8%); for FIT/FOBT, adherence among commercially insured patients (42.3%) was lower than other payer types (47.4-47.9%). Regression analyses confirmed significantly higher FU-CY adherence (p < .001) for mt-sDNA across payer types, sex, and race/ethnicity. Within 180 days, FU-CY rates ranged from 62.7%-74.9% for mt-sDNA versus 36.1%-42.5% for FIT/FOBT. CONCLUSION:In this large national study, adherence to FU-CY was substantially higher following mt-sDNA versus FIT/FOBT across payer types, with notably higher completion within 180 days for mt-sDNA test.

Testicular cancer (TC) is one of the most prevalent cancers among young adult (YA) males. TC can have significant physical and psychosocial impacts on patients, however limited research has focused on the experiences of their young partners. Thus, the aim of this study was to explore the lived experiences of partners of individuals diagnosed with TC as YAs. This study used an interpretive phenomenological research design. Three focus groups with 4–5 participants per group were conducted with partners of individuals diagnosed with TC as YAs (n = 13; 100

BACKGROUND:Data on the safety profiles and clinical outcomes of patients with solid tumors and cardiac metastasis treated with immune checkpoint inhibitors (ICIs) are limited. METHODS:This is an international multicenter retrospective study of patients with cancer and cardiac metastasis at baseline. Patients who had received ≥1 dose of ICI were included. Treatment-related adverse events (trAEs) were graded per Common Terminology Criteria for Adverse Event V.5.0. Objective response rates (ORR) were evaluated by Response Evaluation Criteria in Solid Tumors V.1.1 when available. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. RESULTS:Among 110 pts, median age at ICI initiation was 65 (IQR: 59-75). Median follow-up time since ICI initiation was 36 (95% CI: 26 to 51) months. Melanoma (38%, n=42) and non-small cell lung cancer (24%, n=26) were the most common. 68 (62%) patients received ICIs as first-line, and 29 (26%) patients were treated with combination anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen 4. The most common location of cardiac metastasis was in the atria (37%, n=41) and ventricles (35%, n=39). 15 patients (13.6%) had bilateral cardiac/pericardial metastasis, 44 (40%) had left-sided, and 43 (39.8%) had right-sided. At ICI initiation, 21% (n=23) had a cardiac thrombus. Cardiology referrals and cardiac MRIs at the time of cancer diagnosis were completed on 58 (53%) and 52 (47%) patients, respectively. Cardiac events occurred in 40 (36%) patients, including arrhythmias (n=14, 13%), arterial/venous emboli (n=4, 3.6%), and cardiac tamponade (n=3, 2.7%). 53 (47%) patients developed trAEs; most common were colitis/diarrhea (n=16, 15%), dermatitis (n=13, 12%), and hepatitis (n=9, 8.2%). ICI-related major cardiac trAEs occurred in 2 (1.8%) patients. 22 patients (20%) developed grade ≥3 trAE. Patients with multiple cardiac metastases had significantly lower responses to ICI-based regimens compared with patients with single cardiac metastasis (11% vs 63%, p=0.02). For melanoma, ORR, median PFS, and median OS were 38%, 9.0 months, and 28.9 months, respectively. 83% of patients with melanoma had concordant responses in overall disease burden and cardiac disease. 91 patients discontinued ICIs, and the main reason was progression or death in 55 (49%) patients. CONCLUSIONS:Among patients with pre-existing cardiac metastasis, ICIs demonstrated meaningful clinical efficacy with no increase in safety signals. Most patients had concordant responses in the overall disease burden and cardiac mass. Multidisciplinary teams are crucial for the appropriate management of patients with cardiac metastasis.

Enterocolitis is a common immune-related adverse event associated with cancer immunotherapy. Current guidelines inform first-line pharmacologic management of immune checkpoint inhibitor-related enterocolitis; however, treatment in refractory cases is uncertain. We present a case of a 45-year-old woman with refractory immune checkpoint inhibitor-related enterocolitis requiring treatment with a combination of janus kinase inhibition, therapeutic plasma exchange, and fecal microbiota transplantation after failure of several lines of therapy. This is the first report of the combination of upadacitinib, plasma exchange, and fecal microbiota transplant for refractory enterocolitis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer morbidity and mortality worldwide. Common sites of metastases include the lungs, regional lymph nodes, bone, and adrenal glands. Although rare, distant metastases to the cervical lymph nodes have been reported. With better therapies for viral hepatitis, there has been a shift in the landscape of chronic liver disease and the development of HCC with rising prevalence of HCC attributable to metabolic dysfunction-associated steatotic liver disease. In this study, we describe a case of metastatic HCC presenting as cervical lymphadenopathy in a patient with metabolic dysfunction-associated steatotic liver disease in the absence of cirrhosis.

83 Background: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality and third most common cancer in the United States. In 2021, 141,902 new cases of CRC were reported. With recent increases in early onset of CRC incidence, a shift in patterns amongst various demographics has been observed. Together with an estimated 60% increase in burden of CRC globally, it is important to continuously assess the nationwide incidence rates and monitor the changing patterns. In this study, we examined the annual incidence rates of CRC in average risk adults using a large national claims database and report patterns of incidence based on various demographic characteristics. Methods: CRC diagnoses were retrospectively identified from a large national claims database, which covers over 165 million lives and is representative of the U.S. population, for each calendar year during the study period from 2017 to 2023. Individuals aged 45 to 75 years, with an average risk of CRC before each index calendar year were included in the study. Individuals were required to be continuously enrolled in the same health plan for at least 1 year prior to and 1 year following the index year. Annual CRC incidence rates per 100,000 people were calculated for each year from 2017 to 2023 within various subgroups based on baseline demographics. Results: Overall, annual CRC incidences remained consistent during the study period with 186.86 (95% CI, 184.87-188.86) cases in 2017 and 183.40 (95% CI, 181.32-185.5) cases in 2023 per 100,000. Among younger adults aged 45-49 years, the annual CRC incidence increased by 66% from 2017 (92.04 cases/100,000) to 2023 (153.12 cases/100,000). Conversely, annual CRC incidence decreased by 25% between 2017 (328.52 cases/100,000) and 2023 (244.93/100,000) in older adults aged 65-75 years. Over the study period, CRC incidence in men was higher than women with an overall rate ratio (RR) of 1.206 (95% CI, 1.122-1.297). African American adults had higher CRC incidence than White Americans with an overall rate ratio (RR) of 1.216 (95% CI, 1.152-1.283). Conclusions: Based on this large study of national claims data, CRC incidence rates remained relatively stable in the total population among average-risk patients from 2017 to 2023. The continuing increase in recommended CRC screening utilization showed a decreased incidence rate in the older population, while observing increased incidences among younger patients.

PURPOSE:Colorectal cancer (CRC) remains the second leading cause of cancer-related death in the U.S. This study aimed to evaluate national CRC incidence from 2021 to 2024 using a large, multi-payer claims database. METHODS:This retrospective, cross-sectional study used a national multi-payer claims database to estimate annual CRC incidence from 2021 to 2024. Adults aged 45 to 75 years were included if they had no history of CRC diagnosis from 2015 through the year prior to the given calendar year (2021, 2022, 2023, or 2024) and had at least 1 medical or pharmacy event in a 3-year window centered on that year. CRC incidence was defined as a new diagnosis claim during each study year. Annual incidence rates per 100,000 individuals were calculated and stratified by sociodemographic characteristics. Associations between CRC incidence status (new diagnosis vs. no diagnosis) and sociodemographic subgroups were assessed using Pearson's chi-square tests. FINDINGS:From 2021 to 2024, CRC incidence declined from 136.9 to 115.9 per 100,000 among 145 to 161 million eligible individuals, with declines in those aged 50 to 64 (120.8-101.7) and 65 to 75 (203.6-162.5). In contrast, incidence among those aged 45 to 49 increased from 59.5 to 63.1 over the same period. Incidence remained higher in males than females (129.4 vs. 104.3 in 2024), and although it decreased, it remained highest among Black individuals (225.1-156.8). Medicare Advantage enrollees had the highest incidence throughout (276.8-214.0), while those with commercial insurance had one of the lowest (112.8-93.4). Regional differences narrowed from 2021 to 2024 across the Northeast, Midwest, South, and West; CRC incidence status remained significantly associated with region (Pearson's chi-square P < 0.001). CONCLUSIONS:Overall, CRC incidence declined from 2021 to 2024, though rising rates among adults aged 45 to 49 highlight a growing early-onset burden. Associations between CRC incidence status and age, sex, race/ethnicity, insurance type, and region were observed, suggesting disparities that may reflect underlying equity gaps in prevention.

2649 Background: Immune checkpoint inhibitors (ICI) transformed treatment paradigm across cancers. There remain few reliable, clinically accessible predictors of ICI-induced immune related adverse events (irAEs). We derive a novel risk stratification model for irAEs using baseline patient, tumor and treatment variables in a large cohort of patients with advanced melanoma (AM) or non-small cell lung cancer (NSCLC) treated with ICI. Methods: We conducted a multi-centre retrospective observational cohort study of consecutive patients with AM or NSCLC receiving ≥ 1 cycle of single-agent or combination ICI, in any line, 2015 - 2023, in Alberta, Canada. Clinically significant irAEs, defined as those requiring treatment delay or systemic steroids/steroid sparing agents, were identified as outcome of interest. The association between irAEs, overall survival (OS), and time to next treatment (TTNT) was assessed with Cox Proportional Hazards regression. Stepwise logistic regression was used to select and weight baseline variables associated with development of irAEs to derive a predictive risk score. Model validation was carried out on 500 iterations of bootstrapped samples. Harrel’s C-index was calculated and internally validated to ascertain the model’s discriminatory performance. Results: 1,292 total patients were included, 519 (218/489 [44.6%] AM and 301/803 [37.5%] NSCLC) developing a clinically significant irAE. Using a subset of 801 patients with available baseline characteristics, the following variables were identified and weighted for creation of risk model (risk score attributed): tumor type (NSCLC) (+1), age >60 (+1), ECOG ≥1 (-1), BMI ≥ 25 (+1), ICI after first line (-1), combination ICI (+4), >10 cycles of ICI (+2), albumin level < LLN (+2), adrenal metastasis (+1), multiple sites of metastasis (-1). Patients were stratified into 3 irAE risk groups based on combined score: low (n = 230, risk score ≤ 0), intermediate (n = 412, risk score 1-2), high (n = 159, risk score ≥3). The risk model performed well with an optimism-corrected c-index of 0.707 in internal validation, and strong association with odds of irAE occurrence (Table). The development of irAE was associated with an improvement in OS (HR 0.48, 95% CI 0.41-0.44, p<0.001), with a median OS of 34.3 (95% CI 28.8-39.6) months compared to 12.0 (95% CI 10.6-14.3) months for those who did not develop an irAE. Similar robust stratification was also seen with TTNT. Conclusions: We presented and internally validated, a simple risk stratification tool that utilizes readily available baseline patient, tumor, and treatment characteristics to robustly stratify risk of irAE development. [Table: see text]

Abstract Background Despite an expanding armamentarium of medical treatment options, the 10-year cumulative risk of colectomy for patients with ulcerative colitis (UC) remains 5-10%. Surgery for UC is associated with a substantial burden of mortality. A previous meta-analysis of population-based studies found that postoperative mortality was 0.7% of patients undergoing elective surgery and 5.3% of patients undergoing emergent colectomy. Aims Given improvements in managing acutely ill patients with UC, we aimed to evaluate contemporary rates of postoperative mortality following colectomy. Methods We analyzed data in the National Inpatient Sample (NIS) for 2016-2020. The NIS is an all-payer administrative health database, capturing information from ampersand:003E7 million inpatient admissions at ampersand:003E1000 hospitals across the United States annually. All analyses were weighted to account for the complex stratified survey design. Adult patients (≥18 yrs) with a primary diagnosis of UC undergoing colectomy were identified with ICD-10 coding. Rates of in-hospital postoperative mortality were calculated, and predictors of mortality were evaluated in survey-adjusted logistic regression. Results A total of 8570 hospitalizations for patients with UC undergoing colectomy were included. Mean age at colectomy was 44.5 years and 47% of patients were female. Emergency colectomy was performed in 38.2% [95% CI: 35.9%, 40.7%] of patients, and was attempted laparoscopically in 55.9% [53.1%, 58.7%]. Overall mortality from 2016-2020 was 1.2% [0.8%, 1.9%], but was 0.2% [0.1%, 0.8%] for elective surgery and 2.9% [1.9%, 4.5%] for emergent surgery. Stratified rates of mortality are summarized in Table 1. In multivariable analysis, age was not an independent predictor of mortality but laparoscopic surgery (adjusted odds ratio 0.24 [0.06-0.98], p=0.047) and elective resection (aOR 0.16 [0.04-0.68], p=0.01) were associated with a lower risk of postoperative death. Conclusions Approximately 1 in 100 patients undergoing colectomy for UC will die postoperatively. This risk is highest in comorbid patients undergoing open laparotomy or emergency colectomy. The risk of mortality in both emergent and elective settings is lower than previously reported. Table 1. Stratified risks of mortality after colectomy for ulcerative colitis Funding Agencies None

Background: Colorectal cancer is the third most common malignancy globally. Early-onset colorectal cancer (EOCRC) is becoming a growing healthcare focus globally, particularly in North America. We estimated trends in incidence, mortality, and disability-adjusted life years (DALYs) for EOCRC in Canada between 1990 and 2019. Methods: We used the Global Burden of Diseases Study to evaluate trends in incidence, mortality, and DALYs for EOCRC in Canada between 1990 and 2019. Rates were estimated per 100,000 persons at risk with associated uncertainty intervals (UIs). Annual percentage changes (APC) were estimated using joinpoint regression with 95% confidence intervals (CIs). Results: In 2019, the incidence, mortality, and DALYs rates for EOCRC were 10.89 (95% UI 8.09, 14.34), 2.24 (95% UI 2.00, 2.51), and 111.37 (95% UI 99.34, 124.78) per 100,000 individuals, respectively. Incidence increased during the study period by 1.12%/year (95% CI 1.03%, 1.22%; p < 0.001). The largest increase in incidence in EOCRC occurred between 1990 and 2007, with an APC of 2.23% (95% CI 2.09%, 2.37%; p < 0.001). Mortality (APC 2.95%, 95% CI 1.89%, 4.02%; p < 0.001) and DALY (APC 2.96%, 95% CI 1.84%, 4.09%; p < 0.001) rates increased for males between 2001 and 2006. Conclusions: Our study reveals a substantial burden in EOCRC in Canada, with a significant increase in incidence.

BackgroundBone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival.Materials and methodsA retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs.ResultsA total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05–1.53, p=0.01).ConclusionMetastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.

BackgroundThe association between objective imaging response and first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in routine practice.MethodsWe conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from August 2013-May 2020 in Alberta, Canada. The primary outcome was likelihood of RECIST v1.1 assessed objective imaging response between patients receiving anti-programmed cell death protein 1 (anti-PD1) monotherapy and those receiving combination ipilimumab-nivolumab. Secondary outcomes were identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT).Results198 patients were included, 41/198 (20.7%) had complete response, 86/198 (43.4%) had partial response, 23/198 (11.6%) had stable disease, and 48/198 (24.2%) had progressive disease. Median OS was not reached (NR) (95% CI 49.0-NR) months for complete responders, NR (95%CI 52.9-NR) months for partial responders, 33.7 (95%CI 15.8-NR) months for stable disease, and 6.4 (95%CI 5.2–10.1) months for progressive disease (log-rank p<0.001). Likelihood of objective imaging response remained similar between anti-PD1 monotherapy and ipilimumab-nivolumab groups (OR 1.95 95%CI 0.85–4.63, p=0.121). Elevated LDH level (OR 0.46; 95%CI 0.21–0.98, p=0.043), mucosal primary site (OR 0.14; 95%CI 0.03–0.48, p=0.003), and BRAF V600E mutation status (OR 0.31; 95%CI 0.13–0.72, p=0.007) were associated with decreased likelihood of response.ConclusionNo significant difference in likelihood of imaging response between anti-PD1 monotherapy and combination ipilimumab-nivolumab was observed. Elevated LDH level, mucosal primary site, and BRAF V600E mutation status were associated with decreased likelihood of response. Given that pivotal clinical trials of ipilimumab-nivolumab did not formally compare ipilimumab-nivolumab with nivolumab monotherapy, this work adds context to differences in outcomes when these agents are used. These results may inform treatment selection, and aid in counseling of patients treated with first-line ICI therapy in routine clinical practice settings.

Importance Immune-related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) therapy reportedly improve overall survival (OS) in patients with non-small cell lung cancer (NSCLC). However, studies have been small and the association between irAE severity and OS remains poorly defined.Objective To examine the association between irAEs and their severity with OS in patients with locally advanced or metastatic NSCLC receiving ICIs.Design, Setting, and Participants This retrospective observational cohort study included patients with NSCLC receiving ICIs between March 1, 2014, and November 30, 2021, with follow-up until March 31, 2023. Data analysis was completed April 26, 2023. The Alberta Immunotherapy Database, a provincial, multicenter cohort, was used to capture data from patients receiving ICIs in Alberta, Canada. Participants included 803 patients 18 years or older who received at least 1 cycle of ICI (alone or with chemotherapy), agnostic to treatment line.Exposure Developing an irAE mandating delay or discontinuation of ICI therapy and/or systematic corticosteroids for management of toxic effects (hereinafter referred to as clinically meaningful irAEs).Main Outcomes and Measures The primary outcome was association between irAEs and OS according to Kaplan-Meier analysis. Clinically meaningful irAEs were identified. Patients with poor prognosis (survival <3 months) who may have died prior to irAE development were excluded from OS analysis, mitigating immortal time bias. Adjusted Cox proportional hazards regression analyses ascertained variables associated with OS.Results Among the 803 patients included in the analysis, the median age of patients with irAEs was 69.7 (IQR, 63.1-75.2) years and the median age of those without irAEs was 67.5 (IQR, 60.4-73.3) years, with comparable sex distribution (139 of 295 men [47.1%] and 156 of 295 women [52.9%] with irAEs vs 254 of 505 men [50.3%] and 251 of 505 women [49.7%] without irAEs). Mitigating immortal time bias (n = 611), irAEs were associated with OS (median OS with irAEs, 23.7 [95% CI, 19.3-29.1] months; median OS without irAEs, 9.8 [95% CI, 8.7-11.4] months; P < .001). No OS difference was associated with treatment in hospital vs as outpatients for an irAE (median OS, 20.8 [95% CI, 11.7-30.6] vs 25.6 [95% CI, 20.1-29.8] months; P = .33). Developing irAEs remained associated with OS in the total cohort after Cox proportional hazards regression with known prognostic characteristics (hazard ratio, 0.53 [95% CI, 0.40-0.70]; P < .001).Conclusions and Relevance In this cohort study of 803 patients with locally advanced or metastatic NSCLC receiving ICIs, developing a clinically meaningful irAE was associated with improved OS. This association was not compromised by hospitalization for severe toxic effects. Whether and how ICI therapy resumption after an irAE is associated with OS warrants further study.

Abstract Background Colorectal cancer is the third most common malignancy and remains a leading cause of potentially preventable morbidity and mortality. Early-onset colorectal cancer (EOCRC) is a growing public health focus, particularly in North America, where incidence rates have increased over time. Aims Recognizing that EOCRC affects patients in the prime of their life, we aimed to estimate the impact of EO-CRC on disability-adjusted life years (DALYs) lost in Canada between 1990 and 2019. Methods We used the Global Burden of Diseases (GBD) Study to assess temporal trends in incidence, mortality and DALYs for EOCRC (patients ampersand:003C50 years old) in Canada between 1990 and 2019. Point estimates are available from http://ghdx.healthdata. org/gbd-results-tool. Rates were estimated per 100 0000 individuals at risk and stratified by age and sex. Annual percentage changes (APC) were estimated using joinpoint regression with 95% confidence intervals (CIs). Results In 2019, the incidence, mortality and corresponding DALYs rates for EOCRC were 15.67 (95% CI 11.58, 20.81), 3.19 (95% CI 2.81, 3.61), and 161.88 (95% CI 142.50, 183.53) per 100,000 individuals, respectively. Overall incidence increased significantly during the study period by 1.12%/year (95% CI 0.91%, 1.62%). An analysis of the temporal trends demonstrates that the most significant increase in incidence in EOCRC occurred between 2000 - 2006 with an APC of 3.19% (95% CI 2.40%, 3.99%), which was primarily driven by an increased incidence in men. Mortality (APC 3.30%, 95% CI 2.41%, 4.19%) and DALYs (APC 3.28%, 95% CI 2.34%, 4.22%) for EOCRC also significantly increased for males between 2001 - 2006. Conclusions Our study reveals a substantial burden in early-onset colorectal cancer in Canada, with a significant increase in incidence over time and over 160 DALYs/100,000 population. Figure 1: Incidence (A), Mortality (B) and DALYs (C) for EOCRC in Canada between 1990 and 2019 with 95% CIs. Funding Agencies None